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Background  Interferon regulatory factor-1 (IRF1) affects the proliferation of colorectal cancer (CRC). Recombinant interferon inducible protein 35 (IFI35) participates in immune regulation and cell proliferation. The aim of the study was to examine whether IRF1 affects the radiation sensitivity of CRC by regulating IFI35.    Methods  CCL244 and SW480 cells were divided into five groups: blank control, IFI35 upregulation, IFI35 upregulation control, IFI35 downregulation, and IFI35 downregulation control. All groups were treated with X-rays (6 Gy). IFI35 activation by IRF1 was detected by luciferase reporter assay. The GEPIA database was used to examine IRF1 and IFI35 in CRC. The cells were characterized using CCK-8, EdU, cell cycle, clone formation, flow cytometry, reactive oxygen species (ROS), and mitochondrial membrane potential. Nude mouse animal models were used to detect the effect of IFI35 on CRC.    Results  IRF1 can bind to the IFI35 promoter and promote the expression of IFI35. The expression consistency of IRF1 and IFI35 in CRC, according to GEPIA (R = 0.68,  p  < 0.0001). After irradiation, the upregulation of IFI35 inhibited cell proliferation and colony formation and promoted apoptosis and ROS, while IFI35 downregulation promoted proliferation and colony formation and reduced apoptosis, ROS, and mitochondrial membrane potential were also reduced. The in vivo experiments supported the in vitro ones, with smaller tumors and fewer liver metastases with IFI35 upregulation.    Conclusions  IRF1 can promote IFI35 expression in CRC cells. IFI35 is involved in the regulation of radiosensitivity of CRC cells and might be a target for CRC radiosensitization.

IFI35 is involved in the regulation of the radiosensitivity of colorectal cancer cells